Vessel flow control devices and methods

ABSTRACT

Systems and methods for treating an afflicted vessel and/or vessel associated with an afflicted tissue of a mammalian patient are presented herein. In particular, devices for the control of flow rate and/or pressure within a vessel of a mammalian patient, and methods of treating an afflicted vessel and/or a vessel associated with an afflicted tissue using the devices are presented herein.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a divisional of U.S. application Ser. No.15/389,253 filed Dec. 22, 2016, which application is a continuation ofU.S. application Ser. No. 13/958,313 filed Aug. 2, 2013, now U.S. Pat.No. 9,561,035, which application claims priority to U.S. ProvisionalPatent Application No. 61/679,613, which was filed on Aug. 3, 2012, andis entitled Vessel Flow Control Devices and Methods. The contents of theabove-mentioned patent applications are hereby incorporated by referencein their entirety.

FIELD OF THE INVENTION

Aspects of the present invention relate to systems and methods relatedto the treatment of an afflicted vessel and/or vessel associated with anafflicted tissue of a mammalian patient. More specifically, the presentinvention relates to devices for the control of flow rate and/orpressure within a vessel of a mammalian patient, and methods of treatingan afflicted vessel and/or a vessel associated with an afflicted tissueusing the devices.

BACKGROUND OF THE INVENTION

A variety of afflictions such as peripheral vascular disease, ischemicstrokes, and various other infarctions such as myocardial infarctions,pulmonary infarctions, splenic infarctions, limb infarctions, andavascular necrosis of bone tissue, are associated with blockages ofblood vessels in a human patient, usually due to thrombi (blood clots)or excessive plaque buildup. Because the tissues associated with a bloodvessel typically rely upon that vessel for a continuous supply of oxygenand nutrients, a blockage of that vessel create stresses on theseassociated tissues, as well as the vascular tissues themselves. As aresult, effective treatment of an affliction associated with a blockageof a blood vessel may be complicated by the response of the weakenedvascular tissues to the restored blood flow, and the associatedelevation of flow velocity and blood pressure. The treatment of ischemicstrokes presents a particularly poignant example of the interplay of thecondition of the vascular tissues and the outcome of a treatment.

Ischemic strokes, defined herein as the rapid loss of a brain functiondue to a sudden disruption of the brain's blood supply due to a bloodclot, are a leading cause of death worldwide. Those fortunate enough tosurvive an ischemic stroke may still face significant losses of brainfunction such as loss of the ability to move one or more limbs on oneside of the body, loss of the ability to understand or formulate speech,and/or an inability to see one side of the visual field. Currenttreatments for ischemic strokes must be completed within 3 to 6 hours ofthe stroke due to the associated weakening of the brain vasculartissues. Strokes associated with the disruption of flow withinrelatively large circulatory vessels must be treated quickly due to thelarger area of the brain infracted, the resultant lower coverage ofblood flow to the surrounding tissue from collateral vessels, as well asthe potentially devastating and significant loss of function.

If the stroke is not treated within this relatively brief window ofopportunity, removal of the clot to restore blood flow carries with it asignificant risk of a secondary hemorrhagic event resulting inadditional brain damage or death of the patient. As a result, a highproportion of physicians are relatively reluctant to remove blood clotsoutside of this treatment window, and patients are instead forced tocope with the functional deficits associated with the loss of brainfunction associated with the stroke event. Unfortunately, currenttreatment methods are unable to control the rate at which blood pressureand flow rate are restored to ischemic brain tissues and associatedweakened blood vessels.

The use of current treatment methods are further limited by the inherentdifficulty in pin-pointing the time at which a stroke occurred, as wellas the challenge of transporting a patient to a facility capable ofimplementing one of these current treatment methods. For example,patients presenting with a stroke upon awakening from sleep are notstrong candidates for current treatment methods due to the inability toidentify the time of onset of the stroke. The time elapsed during astroke event, the time taken to recognize that a stroke is occurring,the time taken to signal a need for assistance, the time taken formedical personnel to reach the patient, the time taken to transfer thepatient to a treatment facility, and the time taken to diagnose thestroke condition all narrow the already-brief window of opportunity fortreatment using existing methods. As a result, a significant number ofpatients are not viable candidates for treatment using existing methods.

There exists a need in the art for a device capable of controlling theflow rate and/or pressure within an afflicted vessel and/or a vesselassociated with an afflicted tissue. A need in the art further existsfor a method of treating an afflicted vessel and/or a vessel associatedwith an afflicted tissue using the device to vary the flow rate and/orpressure within the vessel as a treatment and/or in conjunction with anadditional treatment.

BRIEF SUMMARY OF THE INVENTION

In one aspect, a vessel flow control device for controlling a flow rateand/or a pressure within a vessel of a mammalian patient during atreatment is provided. The device includes a variable occlusion elementthat assumes a plurality of occlusion states. Each occlusion state hasan occlusion factor ranging from about 5% to about 100%, and theocclusion factor is defined as the percentage of the lumencross-sectional area occluded by a cross-sectional area of the variableocclusion element. For example, the occlusion factor of 100% correspondsto a complete blockage of flow through the vessel. The device issituated within a lumen of the vessel.

In another aspect, a vessel flow control device for controlling a flowrate and/or a pressure within a vessel of a mammalian patient during atreatment is provided. The vessel flow control device includes at leastone balloon situated within a lumen of the vessel. The balloon includesa cylindrical body, a tapered proximal end projecting proximally fromthe body and ending in a proximal opening, and a tapered distal endprojecting distally from the body opposite to the proximal end andending in a distal opening. The balloon also includes an inner membraneformed into a closed cylindrical shape enclosing a cylindrical lumen;the lumen extends from the proximal opening to the distal opening of theballoon. In addition, the balloon includes an outer membrane sealed tothe inner membrane at the proximal end and at the distal end. Together,the outer membrane and inner membrane enclose an essentially toroidalvolume. In this aspect, the balloon is inflated and/or deflated toassume a plurality of occlusion states with an occlusion factor rangingfrom about 5% to about 100%.

In an additional aspect, a vessel flow control device for controlling aflow rate and/or a pressure within a vessel of a mammalian patientduring a treatment is provided. The vessel flow control device includesa proximal balloon and a distal balloon. The balloons are situatedwithin a lumen of the vessel at a separation distance ranging from about1 inch to about 3 inches. The proximal balloon and the distal ballooneach include a cylindrical body, a tapered proximal end projectingproximally from the body and ending in a proximal opening, and a tapereddistal end projecting distally from the body opposite to the proximalend and ending in a distal opening. The proximal balloon and the distalballoon each further include an inner membrane formed into a closedcylindrical shape enclosing a cylindrical lumen extending from theproximal opening to the distal opening. The proximal balloon and thedistal balloon also further include an outer membrane sealed to theinner membrane at the proximal end and at the distal end; the outermembrane and inner membrane enclose an essentially toroidal volume. Theproximal balloon and the distal balloon each is inflated and/or deflatedto assume a plurality of occlusion states with an occlusion factorranging from about 5% to about 100%.

In another additional aspect, a method of treating an afflicted regionof a vessel of a mammalian patient is provided. The method includessituating a vessel flow control device within a lumen of the vesselupstream of the afflicted region. The device includes a variableocclusion element that assumes a plurality of occlusion states; eachocclusion state has an occlusion factor ranging from about 5% to about100%. The method further includes configuring the device to assume aninitial occlusion state with an occlusion factor of 100%, and graduallyconfiguring the device to assume at least one intermediate occlusionstate and a final occlusion state. Each successive intermediateocclusion state has a lower occlusion factor than the previousintermediate occlusion state, and the final occlusion state has anocclusion factor of about 5%. The device is gradually configured fromthe initial occlusion state to the final occlusion over a predeterminedtreatment period.

In yet another addition aspect, a vessel flow control device forcontrolling a flow rate and/or a pressure within a vessel of a mammalianpatient during a treatment is provided. The vessel flow control deviceincludes a stent device that includes a coated expandable cylindricalelement enclosing a biodegradable material that forms a channel throughwhich a vessel flow may pass when the material is biodegraded.

While multiple embodiments are disclosed, still other embodiments of thepresent disclosure will become apparent to those skilled in the art fromthe following detailed description, which shows and describesillustrative embodiments of the disclosure. As will be realized, theinvention is capable of modifications in various aspects, all withoutdeparting from the spirit and scope of the present disclosure.Accordingly, the drawings and detailed description are to be regarded asillustrative in nature and not restrictive.

BRIEF DESCRIPTION OF THE DRAWINGS

The following figures illustrate various aspects of the invention.

FIG. 1 is a longitudinal cross-sectional view of a balloon device in aninflated position.

FIG. 2 is a longitudinal cross-sectional view of a balloon device in adeflated position.

FIG. 3 is a transverse cross-sectional view through the balloon body astaken through section line 4-4 in FIG. 1.

FIGS. 4A-4B are transverse cross-sectional views of the toroidal volumeof a balloon device subdivided into four lobes. FIG. 4A is anillustration of the four lobes of the toroidal volume when the balloondevice is inflated. FIG. 4B is an illustration of the four lobes of thetoroidal volume when the balloon device is deflated.

FIGS. 5A-5B are transverse cross-sectional views of a central passageformed by the deflation of a balloon device. FIG. 5A is an illustrationof the inflated balloon device including a toroidal volume bounded by anouter membrane and an inner membrane. FIG. 5B is an illustration of anexpanded inner membrane and dilated inner lumen.

FIGS. 6A-6B are transverse cross-sectional views of an outer coatingattached to the outer membrane of a balloon device. FIG. 6A illustratesan intact outer coating. FIG. 6B illustrates the outer coating in abiodegraded condition. FIGS. 6C-6D are transverse cross-sectional viewsof an inner coating attached to the inner membrane of a balloon device.FIG. 6A illustrates the intact inner coating. FIG. 6B illustrates theinner coating in a biodegraded condition.

FIG. 7 is a longitudinal cross-sectional view of a balloon deviceconstructed incorporating semi-permeable material on the distal end anda non-permeable material on the proximal end and balloon body.

FIG. 8 is a longitudinal cross-sectional view of a two-balloon device.

FIG. 9 is a flow chart diagram of a method of using a vessel controldevice to treat an afflicted region of a patient.

FIG. 10 is a longitudinal cross-sectional view of a two-balloon devicewith the upstream balloon deflated and the downstream balloon inflated.

FIG. 11 is a longitudinal cross-sectional view of a two-balloon devicewith the downstream balloon deflated and the upstream balloon inflated.

FIG. 12 is a longitudinal cross-sectional view of a balloon deviceconstructed using a semi-permeable material situated around theperimeter of the balloon body.

FIG. 13 is a longitudinal cross-sectional view of a stent device.

FIG. 14 is a transverse cross-sectional view of a stent device.

FIG. 15 is a longitudinal cross-sectional view of a stent device in anopen-flow configuration.

FIG. 16 is a transverse cross-sectional view of a stent device with abiodegraded occlusive member.

FIG. 17 is a schematic diagram of a method of manually controlling avessel flow control device.

FIG. 18 is a schematic diagram of a method of controlling a vessel flowcontrol device using an automated device.

FIG. 19 is a schematic diagram of a method of controlling a vessel flowcontrol device using a feedback control device.

Corresponding reference characters and labels indicate correspondingelements among the views of the drawings. The headings used in thefigures should not be interpreted to limit the scope of the claims.

DETAILED DESCRIPTION

Provided herein are devices for controlling the flow rate and/orpressure within a vessel of a mammalian patient. In general, the devicesin various aspects may occlude the vessel in a controlled manner toimplement a treatment of an afflicted region. For example, in the caseof vascular tissue injury associated with an ischemic stroke, the devicein one aspect may be used to completely occlude the blood flow enteringan area of clot-related vascular damage, also referred to herein as thepenumbra. The device may also be used to gradually restore bloodpressure and blood flow to the region as the injured vascular tissue ishealed. In other aspects, the device may further deliver one or moresubstances to the vascular tissue occluded by the device to aid in therecovery of the vascular tissue during the treatment. In additionalaspects, the devices may further include instrumentation to assess bloodflow and/or blood pressure in the afflicted region of the patient toprovide information regarding the health and/or functional status of thevascular tissue, the degree of occlusion imparted by the device to thevessel, and any other relevant information regarding the condition orflow environment of the afflicted region of the patient.

Also provided herein are methods of using the devices for controllingthe flow rate and/or pressure within a vessel of a mammalian patient. Inone embodiment, the device may be operatively contacted with a vesselassociated with an afflicted region such that the vessel is completelyoccluded initially. The configuration of the device may be graduallyaltered over time to reduce the device-related occlusion within thevessel. The configuration of the device may be altered according to afixed and predetermined scheduled in one aspect, or the configurationmay be altered based on assessments of the health and function of thevessel and/or afflicted tissue, either manually or by means of afeedback-based control system in other aspects.

For example, the device may be operatively contacted with a blood vesselassociated with an ischemic stroke such that the vessel is completelyoccluded. According to a predetermined or feedback-based schedule, theconfiguration of the device may be gradually altered to reduce theocclusion and thereby increase the flow rate and pressure within thevessel. Based on subsequent measurements of the health and function ofthe vessel and/or afflicted tissue, the configuration of the device maybe adjusted to increase the occlusion if the measurements indicatedegradation of the tissue or vessel and to decrease the occlusion if themeasurements indicate the enhanced health and function of the afflictedtissues and associated vessel. In additional aspects, therapeuticcompounds may be introduced into the afflicted area by the device toenhance the health and function of the afflicted tissues and associatedvessel at any time during the treatment, including during full occlusionof the vessel by the device. The other additional aspects, the devicemay further include other means of treating the afflicted tissues. Forexample, in the case of treatment of an ischemic stroke using an aspectof the devices described herein, the device may further includeadditional features that allow the clot associated with the ischemicevent to be removed from the afflicted vessel prior to subsequenttreatment as described herein.

In an aspect, the mammalian patient may be any mammalian organism.Non-limiting examples of mammalian organisms that are suitable patientsin various aspects of the method include mammals from the Order Rodentia(mice); the Order Logomorpha (rabbits); the Order Carnivora, includingFelines (cats) and Canines (dogs); the Order Artiodactyla, includingBovines (cows) and Suines (pigs); the Order Perissodactyla, includingEquines (horses); and the Order Primates (monkeys, apes, and humans). Inanother aspect, the patient is a human.

Any size, type, and/or location of vessel within the mammalian patientmay be treated using the devices and methods described herein withoutlimitation, so long as the device is capable of operatively contactingthe vessel in order to control the flow rate and/or pressure asdescribed herein. In various aspects, the vessel may include anybiological structure, tissue, or organ capable of convectivelytransporting a fluid at a flow rate. Non-limiting examples of vesselsinclude circulatory vessels, urinary tract vessels, digestive tractvessels, respiratory vessels, and ventricular system vessels.Non-limiting examples of circulatory vessels include capillaries,arterioles, venules, arteries, veins, hearts, lymph nodes, and lymphaticvessels. Non-limiting examples of urinary tract vessels include kidneys,ureters, bladders, and urethras. Non-limiting examples of respiratoryvessels include oropharynxes, nasopharynxes, larynxes, tracheas,bronchi, bronchioles, and alveoli.

The diameters of the circulatory vessels may range between about 10 μmand about 2 cm. In an aspect, if the device operatively contacts thevessel by implantation within the vessel, the vessels suitable fortreatment by the device may be limited to those vessels large enough toaccommodate the device and associated equipment including, but notlimited to, a delivery device.

The devices and methods of various aspects may be used as a treatment,or as part of a treatment, for a variety of afflictions. Non-limitingexamples of afflictions amenable to treatment using aspects of thedevice and method include: ischemic strokes and other clot-relatedinfarctions such as myocardial infarctions, pulmonary infarctions,splenic infarctions, limb infarctions, and avascular necrosis of bonetissue, various forms of cancers/tumors, aneurysms, stenosisdissolution, and diabetes-related circulatory afflictions.

Various aspects of the vessel flow control devices and methods of usingthe devices to treat an affliction in a mammalian patient are presentherein below.

I. Vessel Flow Control Device

In various aspects, the vessel flow control device may provide featuresto control the rate of flow and/or the pressure within a vessel in aselected region within a mammalian patient. Typically, this selectedregion may be an afflicted region associated with a vessel and/or anafflicted vessel. Non-limiting examples of vessels within selectedregions include a vessel blocked by a clot or other structure within aninfracted region; or a vessel providing blood to a region of tumortissue. In an aspect, the vessel flow control device provides a numberof useful functions when placed in operative connection with a vessel ofa patient, including, but not limited to: complete obstruction of flowthrough the vessel; restoration of unobstructed flow through the vesselaccording to a predetermined schedule or in response to measurementsrelated to the assessment of the health and/or function of the vessel;controlled release of one or more compounds to provide oxygen,nutrients, and or treatment to the vessel and/or associated region ofthe patient.

a. External Vessel Flow Control Devices

The vessel flow control device may be an external vessel flow controldevice operatively connected to the outside of the vessel of the patientin one aspect. In this aspect, the external vessel flow control devicemay include clamps and any other known suitable mechanical flowrestriction element to releasably restrict flow through the vessel ofthe patient by a physical method. In another aspect, the vessel flowcontrol device may include one or more electrodes applied externally tothe vessel of the patient; activation of the electrodes may stimulatethe contraction of smooth muscle tissue surrounding the vessel,resulting in the restriction of flow through the vessel. In yet anotheraspect, chemical vessel restrictors including, but not limited todopamine and LEVOPHED, as well as chemical vessel dilators including,but not limited to, papaverine, may be administered in a sequence andamount sufficient to induce the constriction and dilation of the vesselaccording to a predetermined schedule.

b. Implanted Vessel Flow Control Devices

In another aspect, the vessel flow control device may be operativelyconnected by implanting the device within the lumen of the vesselupstream of the afflicted region. In this aspect, the device may becapable of reversibly or irreversibly changing shape, resulting in achange in cross-sectional area. At one extreme, the device may assume ashape having a cross-sectional area that completely blocks the lumencross-sectional area, corresponding to an occlusion factor of 100%. Thedevice may also assume a shape having a cross-sectional area thatpartially blocks the lumen cross-sectional area, corresponding to anocclusion factor of less than 100%. At another extreme, the device mayassume a shape having a cross-sectional area that has essentially noblocking effect on the lumen cross-sectional area, corresponding to anocclusion factor of 0%. Occlusion factor, as used herein, describes theratio of the cross-sectional area of vessel flow control device dividedby the cross-sectional area of the vessel lumen expressed as apercentage.

The implanted vessel flow control devices may be implanted within avessel using a delivery device. Any known delivery device may be used tosituate and secure the implanted vessel flow control devices in placeincluding, but not limited to, catheters and guide wires. In aspect, thedelivery device may be selected in order to fit within the vessel to betreated using the device. Non-limiting examples of catheters suitablefor situating the implanted vessel flow control devices within thevessel include: neurovascular catheters; peripheral venous catheter(PVC); central venous catheters; arterial catheters; non-tunneledcatheters including Quinton catheters; tunneled catheters includingHickman catheters, Broviac catheters, Groshong catheters, andperipherally inserted central catheters (PICC or PIC lines); ballooncatheters; balloon-tipped catheters; coaxial Teflon catheters;irrigation catheters; intracardiac catheters; bronchospirometrycatheters; and pulmonary artery catheters including Swan-Ganz catheters.

The delivery device may be operatively attached to the implanted vesselflow control device. In addition, the delivery device may includeelements to enhance the function of the implanted vessel flow controldevice including, but not limited to: tools for expanding or deploying astent-type device; fluid supplies for inflating balloon-type devices;light sources and/or cameras for visualizing the implantation area; andconduits for the delivery of active compounds to treat the vessel. Theconduits may also deliver other compounds including, but not limited tobiodegrading agents to initiate the biodegrading of structural elementsand/or coatings of the implanted vessel flow control devices.

In an aspect, the implanted vessel flow control device may remainattached to the delivery device throughout a treatment of a vessel, andmay further be used to remove at least part of the implanted vessel flowcontrol device upon completion of the treatment. In another aspect, thedelivery device may be detached from the implanted vessel flow controldevice before, during, or after the treatment. In this aspect, theimplanted vessel flow control device may remain implanted within thepatient after completion of the treatment, or at least a portion of theimplanted vessel flow control device may be removed from the patientafter the treatment using a recovery device. Any known recovery deviceknown in the art may be used without limitation including, but notlimited to, a recovery wire and/or a recovery catheter.

If the implanted vessel flow control device remains implanted within thepatient after the completion of the treatment, the implanted vessel flowcontrol device may incorporate additional features to enhance thepost-treatment function of the implanted vessel flow control device. Forexample, the implanted vessel flow control device may include an activecompound such as a clot-inhibiting compound in any known time-releasedform including, but not limited to, a time-release coating that includesthe active compound. In another example, at least a portion of theimplanted vessel flow control device, up to and including the entireimplanted vessel flow control device, may be constructed from abiodegradable material that is resorbed following the treatment.

A biodegradable material, as used herein, refers to any material thatbiodegrades after exposure to the physical, biological, and/or chemicalenvironment within the vessel. The biodegradable material may biodegradespontaneously, or the biodegradable material may biodegrade afterexposure to an extrinsic biodegrading agent introduced into the vessel.In an aspect, the biodegradation may occur by means of a mechanism thatavoids releasing particles of biodegradable material into the vesselthat may cause secondary blockages within the vessel. Non-limitingexamples of suitable mechanisms by which the biodegradation may occurinclude: dissolving, leeching, resorption, and any combination thereof.

The implanted vessel flow control devices may be provided in a varietyof forms without limitation. Non-limiting examples of implanted vesselflow control devices include: balloon devices including at least oneimplanted inflatable/deflatable balloon, stent devices including a stentcapable of expanding/contracting or biodegrading according to apredetermined schedule; and other biodegradable implants capable ofbiodegrading according to a predetermined schedule or in response toexposure to a dissolving agent. The implanted vessel flow controldevices including balloon devices, stent devices, and otherbiodegradable implants are described herein below.

i. Balloon Devices

The implanted vessel flow control device may be a balloon device in oneaspect. FIG. 1 is a longitudinal cross-sectional view of a balloondevice 100 in one aspect. The balloon device 100 may include a balloonbody 102 that has a roughly cylindrical shape when inflated. The balloondevice 100 may further include a tapered proximal end 104 projecting ina proximal direction from the balloon body 102; the proximal end 104further contains a proximal opening 106. The balloon device 100 mayfurther include a tapered distal end 108 containing a distal opening 110projecting in a distal direction from the balloon body 102 opposite tothe proximal end 104.

The balloon 100 may be situated within a lumen 112 of a vessel 114upstream relative to a clot 116 or other obstructive structure using adelivery device 120. The term “upstream”, as used herein, may be definedby the direction of the flow 118 within the lumen 112 of the vessel.When fully inflated, the balloon body 102 may expand to a diameteressentially equal to the diameter of the vessel lumen when fullyinflated, as illustrated in FIG. 1. In this configuration, the balloondevice 100 has an occlusion factor of 100%, and no flow may pass theballoon body 102.

When the balloon device has an occlusion factor of 100%, the region ofthe blood vessel 114 situated downstream of the balloon device 100experiences essentially zero flow speed and relatively low pressure.Without being limited to any particular theory, the low pressure andzero flow speed in this downstream region may provide conditionswell-suited for the recovery and healing of any vascular tissue withinthe downstream region that may be weakened by the formation and/orremoval of the clot 116.

If the clot 116 is removed from the lumen 112, the flow 118 through thevessel 114 may be reestablished up to physiological flow speeds and flowpressures. In an aspect, the balloon device 100 may be deflated asillustrated in FIG. 2 as a longitudinal cross-sectional view, causing areduction in the diameter of the balloon body 102 such that thecross-sectional area of the balloon body 102 no longer fills thecross-sectional area of the lumen 112, resulting in an occlusion factorof less than 100%. In this configuration, the flow 118 within the vessel114 may pass the balloon body 102 in the annular space formed betweenthe balloon body 102 and the lumen 112; this reestablishment of flow inthe vessel 114 results in a rise in the flow rate and pressuredownstream of the balloon device 100. In an aspect, the balloon may bedeflated over a period of time sufficient to allow for the healing ofthe vascular tissues injured by the clot 116. The rate at which theballoon device 100 may be deflated to reestablish flow within the vesselmay be specified using a variety of methods discussed in detail hereinbelow. In another aspect, the deflated balloon may be held in placeusing a delivery device 120 or other tethering device.

a. Inflation/Deflation Features of Balloon Devices

FIG. 3 illustrates a transverse cross-sectional view through the balloonbody 102 of the balloon device 100 as taken along section line 4-4 inFIG. 1. In this aspect, the balloon device 100 is formed from a thinflexible outer membrane 202. The outer membrane 202 may be sealed to theinner cylinder 204 at the proximal end 104 and at the distal end 108.Together, the outer membrane 202 and the inner cylinder 204 enclose atoroidal volume 206 that may enlarge and shrink as the balloon device100 is inflated and deflated.

The inner cylinder 204 further encloses a cylindrical internal volume208 that opens to the proximal opening 106 and the distal opening 110 atopposed ends. In an aspect, a delivery device 210 may be situated withinthe internal volume 208. In this aspect, the delivery device 210 mayprovide a means of situating the balloon device 100 upstream of the clot116 as illustrated in FIG. 1. The delivery device 210 may furtherprovide pneumatic pressure to inflate and/or deflate the balloon device100. Other equipment may also be included or connected to the deliverydevice 210 including, but not limited to flow measurement devices,pressure sensors, temperature sensors, clot ablation or dissolvingdevices, and additional conduits through which additional substances maybe introduced into the region of the lumen 112 situated downstream ofthe balloon device 100. Non-limiting examples of additional substancesinclude: oxygenating compounds, nutrients, compositions for thetreatment of the afflicted region downstream of the balloon device 100,clot-dissolving compounds, vascular dilation compounds, vascularconstriction compounds, and any other suitable substance. A moredetailed description of the delivery device 210, its associatedequipment, and uses are described in detail herein below.

The balloon device 100 may be constructed from any suitablesemi-compliant material known in the art. Non-limiting examples ofsuitable semi-compliant material include ethylene-vinyl acetate,polyvinyl chloride (PVC), olefin copolymers or homopolymers,polyethylenes, polyurethanes, crosslinked low density polyethylenes(PETs), highly irradiated linear low density polyethylene (LDPE),acrylonitrile polymers and copolymers, acrylonitrile blends and ionomerresins. In another aspect, if the osmotic movement of fluid in or out ofthe balloon device 100 is desired, at least a portion of the balloondevice 100 may be incorporated from a semi-permeable material including,but not limited to urethane. In various aspects, as described in detailherein below, a particular portion of the balloon device 100incorporates a semi-permeable material in order to achieve any one of avariety of advantageous properties in use.

In other aspects, the balloon device 100 may comprise alternativedesigns, resulting in different properties, in particular as related tothe changes in cross-sectional area to reduce the occlusion factor. Inthe balloon device 100 illustrated in FIG. 1 and FIG. 2, the vessel flow118 moves through a space formed between the vessel wall 114 and theballoon body 102 when the balloon device 100 is deflated. In anotherembodiment, illustrated in FIGS. 4A and 4B, which are transversecross-sections of the toroidal volume of the balloon device 100A, thetoroidal volume may be subdivided into two or more lobes; four lobes502A-502D are illustrated in FIGS. 4A and 4B. When the balloon device100A is inflated, as illustrated in FIG. 4A, the lobes 502A-502D arepressed tightly against each other, filling the entire cross-sectionalarea of the lumen of the vessel (not shown) and resulting in anocclusion factor of about 100%. When the balloon device 100A isdeflated, as illustrated in FIG. 4B, the lobes 502A-502D may be designedto separate at their respective contact surfaces, forming channels504A-5040 through which the vessel flow (not shown) may pass.

In an additional aspect, as illustrated in FIGS. 5A and 5B which aretransverse cross-sections of the balloon device 100B, the balloon device100B may be designed such that a central passage is formed by thedeflation of the balloon device 100B. As illustrated in FIG. 5A, theinflated balloon device 100B includes a toroidal volume 606 bounded byan outer membrane 602 and an inner membrane 604. The inner membrane 604encloses in inner lumen 608 which is essentially closed when the balloondevice 100B is fully inflated, resulting in an occlusion factor ofessentially 100%. When the balloon device 100B is deflated, asillustrated in FIG. 5B, the inner membrane 604 expands toward the outermembrane 602, thereby dilating the inner lumen 608. This inner lumen 608may function as a conduit to carry vessel flow (not shown) into theregion of the vessel downstream of the balloon device 1008, resulting inan occlusion factor of less than 100%.

b. Balloon Devices with Biodegradable Coatings

In yet another aspect, the balloon device 100C, illustrated in FIGS. 6Aand 6B as transverse cross-sections, may include an outer coating 708attached to the outer membrane 702 of the device 100C. In this aspect,the central volume 706 enclosed by the outer membrane 702 and the innermembrane 704 may remain relatively unchanged during the treatment usingthe balloon device 100C. However, the outer coating 708 may beconstructed of a material that may spontaneously biodegrade under thephysical and chemical conditions characteristic of the vessel 114 inwhich the balloon device is situated in one aspect. In another aspect,the outer coating 708 may incorporate a material that biodegrades uponexposure to a separate biodegrading agent introduced into the vessel114. Regardless of the proximate cause of the biodegrading of the outercoating 708, the reduced cross-sectional area occupied by the balloondevice 100C forms a toroidal space 710 between the outer layer 708 andthe vessel 114 that allows for vessel flow into the lumen volume of thevessel situated downstream from the balloon device 100C.

FIGS. 6C and 6D are transverse cross-sections of a balloon device 100Din another aspect. In this aspect, the balloon device 100G may be acylindrical shell that maintains contact between the vessel 114 and theouter membrane 702 of the device 100G. An inner coating 712 may beattached to the inner membrane 704 of the device 100G. The inner coating712 may reduce the extent of the volume 706 enclosed by the innermembrane 704. In a manner similar to the outer coating 708 describedherein previously, the inner coating 712 may be constructed of amaterial that may spontaneously biodegrade under the physical andchemical conditions characteristic of the vessel 114 or upon exposure toa separate biodegrading agent introduced into the vessel 114. Thebiodegradation of the inner coating 712 results in an increase of theextent of the volume 706 enclosed by the inner layer 704, therebyallowing for vessel flow through the volume 706.

c. Osmotically Active Liquids of Balloon Devices

In one aspect, the balloon device 100 may be introduced by deliverydevice that includes a guide wire situated within an inner lumen of amulti-lumen catheter. The enclosed volumes of the balloon device 100 maybe filled with a liquid introduced by an outer lumen of catheter toinflate the device 100. Any suitable incompressible liquid may be usedto inflate the devices. Non-limiting examples of liquids suitable forinflating the balloon devices include: saline solution, plasma, wholeblood, hydrophilic compounds, dopamine, papaverine, oxygenated fluids,TPA (Tissue Plasminogen Activator) and any other suitable incompressiblefluid.

In an aspect, the concentration of the liquid introduced into the device100 may be selected to be hyperosmotic, isoosmotic, or hypoosmoticrelative to the surrounding blood within the vessel in which the device100 is situated. In this aspect, if the outer membrane of the balloondevice is constructed of a semipermeable material including, but notlimited to, a urethane material, the introduction of the liquid into thedevice 100 may result in the passive movement of fluid into or out ofthe balloon device 100, depending on the tonicity of the liquid insidethe device 100. In an aspect, the tonicity of the liquid inside thedevice 100 may be selected to result in a net movement of fluid into theballoon device, thereby passively maintaining the device 100 in aninflated configuration. In another aspect, the tonicity of the liquidinside the device 100 may be selected to result in a net movement offluid out of the balloon device 100. In this aspect, the net movement offluid out of the device 100 may be used as a passive mechanism by whichvessel flow is reestablished in the vessel. As the fluid is driven fromthe device 100 by the osmotic gradient, the volume of the device 100 maysubsequently shrink gradually over time, resulting in a slowlydecreasing occlusion factor and the gradual reestablishment of vesselflow. The rate of transition to full physiological flow conditions inthe vessel may be specified in part by the degree of tonicity of theliquid introduced into the balloon device 100.

In addition to passively reintroducing vessel flow, the passive movementof fluid out of the balloon device in this aspect may be furtherexploited to deliver compounds to the region in which the device issituated. In another aspect, the liquid introduced into the device 100may further include one or more additional dissolved compoundsincluding, but not limited to, active pharmaceutical compounds,oxygen-bearing compounds, nutrients, clot-dissolving compounds, andother suitable additional compounds. In order to deliver the one or moredissolved compounds to the desired region within the vessel, the balloondevice may incorporate additional design features to implement themovement of fluid out of the device within specified regions of thedevice 100.

For example, as illustrated in the longitudinal cross-sectional view ofFIG. 7, the balloon device 100D may be constructed using asemi-permeable material such as urethane on the distal end 108, andusing a non-permeable material on the remaining balloon body 102 andproximal end 104 portions of the device 100D. If the device 100D isfilled with a liquid 802 having a tonicity that results in the netmovement of fluid out of the device 100D, the construction of the device100D limits the outward movement of fluid 802 to the distal end 108. Ifa dissolved compound 804 is included in the liquid 802, this dissolvedcompound 804 may be carried by the moving fluid 802 preferentially tothe region of the lumen 112 situated downstream of the device 100D. Forexample, if the dissolved compound was a clot-dissolving compound, thedevice 100 may function to dissolve the clot 116 as well as to protectthe lumen 112 and vessel wall 114 from potentially harmful elevatedpressures and flow speeds. In another embodiment, the net movement outof the device 100D may be driven by increased hydrostatic pressurewithin the device 100D in addition to or instead of by osmotic pressure.

In another aspect, the balloon device 100 may be constructed using asemi-permeable material including, but not limited to, urethane situatedaround the perimeter 1302 of the balloon body 102 as illustrated in FIG.12. In this aspect, if the tonicity of the fluid introduced into theballoon device 100G results in a net outward movement of fluid from thedevice 100G, the expelled fluid 1304 may be situated in the gap betweenthe perimeter 1302 of the balloon body and the vessel wall 114. Withoutbeing limited to any particular theory, this fluid movement may inhibitthe adhesion of the balloon body 102 to the vessel wall 114 and/orinhibit the formation of thrombi within this area of contact. If theliquid 802 introduced into the balloon device 100G further includes adissolved anti-adhesion compound in an aspect, the fluid movement maydeliver the anti-adhesion compound between the perimeter 1302 and vesselwall 114, further inhibiting adhesion and/or clot formation. In anotherembodiment, the fluid movement out of the device 100G may result fromelevated hydrostatic pressure within the device 100G, in addition to orinstead of from osmotic pressure.

d. Multi-Balloon Devices

In an aspect, the implanted vessel flow control device may be amulti-balloon device. In one aspect, the multi-balloon device mayinclude an upstream balloon and at least one downstream balloonssituated in the vessel downstream of the afflicted area. For example,within a vessel that bifurcates into two downstream branches, theupstream balloon may be situated upstream of the bifurcation, and eachof downstream balloons may be situated within a branch of the vesseldownstream of the bifurcation point.

As illustrated in FIG. 8, a two-balloon device 900 may include twoballoons 100E and 100F similar in design to the single balloon devices100 described herein previously. In this aspect, the two balloons arearranged sequentially along the length of a multi-segmented catheter 902that includes three segments: a large-diameter segment 904, anintermediate diameter segment 906, and a small diameter segment 908. Thesmall diameter segment 908 nests within the intermediate diametersegment 906 and the intermediate diameter segment 906 nests within thelarge-diameter segment 904. Thus, the segments 904, 906, and 908 may becoaxially arranged with each other such that the small diameter segment908 is coaxially located within the intermediate diameter segment 906,which is coaxially located within the large diameter segment 904. Theproximal end 910 of the multi-segment catheter 902, which includes allthree segments 904, 906, and 908, extends out past the region at whichthe catheter 902 was introduced into the vessel lumen 112 of thepatient. The proximal balloon 100F is sealed to the large-diametersegment 904 at location 906 and is further sealed to the intermediatediameter segment 906 at location 912. The distal balloon 100E is sealedto the intermediate diameter segment 906 at location 914 and is furthersealed to the small diameter segment 908 at location 916. In thisaspect, the two balloons 100E and 100F may be separated by a distanceranging from about 1 inch to about 3 inches.

With this arrangement, the proximal balloon 100F may be inflated ordeflated by introducing or removing a fill liquid as described hereinabove via a fluid pathway defined between an outer circumferentialsurface of the intermediate-diameter segment 906 and an innercircumferential surface of the large-diameter segment 904. Similarly,the distal balloon 100E may be inflated or deflated by introducing orremoving a fill liquid via a fluid pathway defined between an outercircumferential surface of the small-diameter segment 908 and an innercircumferential surface of the intermediate diameter segment 906. Inthis aspect, each balloon 100E or 100F is hydraulically independent ofthe other balloon, providing the ability to inflate or deflate oneballoon device independently of the other device. In use, thishydraulically independent design may result in at least several usefulfeatures for the device 900.

In one aspect, illustrated in the longitudinal cross-sectional view ofFIG. 10, the proximal balloon 100F may be deflated while the distalballoon 100E is maintained in an inflated configuration. Thisconfiguration of the device 900 may provide access to the region 112downstream of the proximal balloon 100F, which may include the afflictedregion of the patient containing a clot or other abnormality. In thisconfiguration, the afflicted region of the lumen 112 may be renderedaccessible to additional instruments such as delivery devices, oraccessible to contact by treatment compounds such as clot-dissolvingsubstances, by oxygenated blood and/or nutrients, and/or any othersuitable instrument or compound. By maintaining the distal balloon 100Ein an inflated configuration, the upstream flow 918 may contact theafflicted region 112 without exposing the afflicted region 112 to highflow rates. In another aspect, the configuration illustrated in FIG. 10may be used to prevent the formation of thrombi within the contact areabetween the proximal balloon 100F and the vessel wall 114.

In another aspect, illustrated in the longitudinal cross-sectional viewof FIG. 11, the distal balloon 100E may be deflated while the proximalballoon 100F is maintained in an inflated configuration. Thisconfiguration of the device 900 may provide fluidic contact between theafflicted region 112 and the vessel region downstream of the distalballoon 100E. In this configuration, the afflicted region 112 andsurrounding tissues may be rendered accessible to additional instrumentssuch as additional delivery devices introduced into the vessel lumendownstream of the device 900, or accessible to contact by treatmentcompounds such as clot-dissolving substances, by oxygenated blood and/ornutrients, and/or any other suitable instrument or compound. Bymaintaining the proximal balloon 100F in an inflated configuration, theupstream flow 918 remains sheltered from the physiological blood flow,thereby preventing the exposure of the afflicted region of the lumen 112to the elevated physiological pressures and flow rates. In anotheraspect, the configuration illustrated in FIG. 11 may be used to preventthe formation of thrombi within the contact area between the distalballoon 100E and the vessel wall 114.

In addition to the advantages of the dual-balloon device 900 describedherein above, this arrangement may further enhance the degree of controlover the flow rate and pressure experienced within the afflicted region112 of the vessel. For example, the distal balloon 100E may bedifferentially inflated or deflated relative to the proximal balloon100F in order to increase or decrease the pressure experienced with theafflicted region 112. Other combinations of differential inflation ordeflation of the balloons 100E and 100F are possible and may result inadditional degrees of enhanced control over the flow conditionsexperienced by the afflicted region 112 of the vessel.

In another aspect, the small diameter segment 908 extends uninterruptedfrom the upstream side to the downstream side of the device 900, asillustrated in FIG. 8. As a result, the small diameter segment 908provides a bypass of the device 900 from the proximal side to the distalside through which a variety of substances may be provided to the vesseldownstream of the device 900. For example, the small diameter segment908 may be used to deliver one or more additional substances including,but not limited to, oxygenated blood, nutrients, artificial blood,therapeutic compounds, and any other suitable compound to the region ofthe vessel downstream from the device. Because the device 900 typicallycompletely blocks vessel flow for at least a portion of its workinglifetime, the vessel and tissues downstream of the device 900 may sufferoxidative, nutritive, and other physiological stresses due to thetreatment of the patient using the device 900. By introducing the one ormore additional substances to the region of the vessel situateddownstream of the device 900, the vessel in this region and itsassociated tissues may be maintained in a physiologically viable stateduring the course of treatment using the device 900.

e. Balloon Instrumentation

In another aspect, the balloon devices 100 and/or 900 described hereinabove may additionally include instrumentation to measure relevantphysical and chemical conditions in the vessel regions upstream,immediately adjacent, and/or downstream of the device 100 or 900.Non-limiting examples of suitable physical and chemical conditionsinclude: flow rate, pressure, temperature, pH, hematocrit, plateletcount, electrical activity, cytokine, glucose, oxygen, carbon dioxide,and other relevant compound concentrations. Any known instrumentationmay be incorporated into the balloon devices 100 and/or 900, as long asthe selected instrumentation is biocompatible and of suitable size forintroduction into the vessel of the patient.

Non-limiting examples of suitable instrumentation for incorporation intothe devices 100 and/or 900 in various aspects include thermocouples formeasuring temperature, piezoelectric pressure sensors, heated velocitysensors, and any other known suitable miniature sensor. For example, aheated velocity sensor may include a heated or cooled strip of materialupon which one or more strain gages are mounted. The flow rate may bedetermined by assessing the effect of conductive heating or coolinginduced by the vessel flow on the strain gage resistance.

In various aspects, the instrumentation may be mounted at any locationrelative to the balloon device without limitation. In one aspect, twopressure sensors may be situated such that one pressure sensor measuresthe pressure upstream of the balloon device 100 or 900, and the secondpressure sensor measures the pressure downstream of the balloon device.A comparison of the upstream and downstream pressures may provide anindication of the flow vessel flow conditions. For example, if theupstream pressure sensor indicates a higher pressure than the downstreampressure sensor, this differential may be interpreted as confirmationthat the vessel flow is significantly occluded by the device 100 or 900.In this example, an equalization of the upstream and downstreampressures may be expected as the occlusion diminishes.

ii. Stent Devices

In another aspect, the vessel flow control device may be a stent device.FIG. 13 is a longitudinal cross-section of a stent device 1400 in anaspect. The stent device 1400 may include a stent body 1402 that has aroughly hollow cylindrical shape when deployed. The stent body 1402 mayinclude a proximal end 1404 containing a proximal opening 1406, and adistal end 1408 containing a distal opening 1410.

In an aspect, the stent 1400 may be constructed using any material knownto be suitable for stent construction including, but not limited tostainless steel; NITINOL; bio-resorbable materials including PGA, PDS,PGA-PCL, and PLLA; biodegradable materials including enteric coatingmaterials and hydrogel materials; PEEK; any other known stent materials,and any combination thereof.

The stent 1400 may be situated within a lumen 112 of a vessel 114upstream relative to a clot 116 or other obstructive structure; upstreammay be defined by the direction of the flow 118 in the lumen 112. Inanother aspect the stent 1400 may be situated over the clot 116 or otherobstructive structure; in this aspect, the stent 1400 may compress theclot 116 against the wall of the vessel 114. When fully deployed, thestent body 1402 may expand to a diameter essentially equal to thediameter of the vessel lumen as illustrated in FIG. 13.

In addition, the stent 1400 may include an occlusive element 1412 toimpede the vessel flow 118 to a predetermined degree, resulting in apredetermined occlusion factor. The occlusive element 1412 may be anystructural feature within the stent 1400 capable of occluding the vesselflow 118. As illustrated in FIG. 13, the occlusive element 1412 may bean approximately hourglass-shaped solid structure that narrows to achannel 1414 through which the vessel flow may pass. In an aspect, theocclusive element 1412 may be fabricated from a biodegradable materialcapable of biodegrading and/or resorbing over a predetermined period,resulting in a gradual decrease of the occlusion factor, and acommensurate increase in vessel flow, in accordance with a predeterminedschedule. In another aspect, the occlusive element 1412 may befabricated from a semipermeable membrane filled with an osmoticallyactive fluid that gradually releases fluid into the vessel, resulting inthe gradual widening of the channel 1414, thereby decreasing theocclusion factor of the stent 1400. In another aspect, the entire stent1400 may be constructed from at least one biodegradable material. Inthis aspect, the entire stent 1400 may partially or completelybiodegrade and/or resorb over time.

FIG. 14 is a transverse cross-sectional view of the stent 1400 taken atsection A-A as denoted in FIG. 13. FIG. 14 illustrates the occlusiveelement 1412 situated within the stent 1402 as well as the channel 1414formed within the center of the occlusive element 1412. In thisconfiguration, the stent device 1400 has an occlusion factor of about100% or substantially 100%, and no flow or substantially no flow maypass the stent body 1402. FIG. 15 is a longitudinal cross-section of thestent 1400 illustrated in FIG. 13 with reduced occlusive element 1412and widened channel 1414. In this configuration, the occlusion factor ofthe stent device 1400 may be significantly reduced to a level as low asabout 5%, thereby allowing a significantly higher vessel flow 118through the vessel lumen 112. Detailed descriptions of various aspectsof the design and characteristics of the occlusive element 1412 areprovided herein below.

Referring back to FIG. 13, if the clot 116 is removed from the lumen112, the flow 118 through the vessel 114 may be reestablished up tophysiological flow speeds and flow pressures. In an aspect, the stent1400 may be gradually collapsed as illustrated in the longitudinalcross-sectional view of FIG. 15, causing a reduction in the diameter ofthe stent body 1402 such that the cross-sectional area of the stent body1402 no longer fills the cross-sectional area of the lumen 112,resulting in an occlusion factor of less than 100%. In thisconfiguration, the flow 118 within the vessel may pass the stent body1402 in the annular space formed between the stent body 1402 and thelumen 112; this establishment of flow in the vessel 114 results in arise in the flow rate and pressure downstream of the stent device 1400.The gradual collapse of the stent 1400 may be implemented in a passivestructure that spontaneously collapses over time, or the gradualcollapse of the stent may be actively controlled by a practitioner invarious aspects. For example, the stent 1400 may be constructed fromNITINOL memory wire in a configuration capable of collapsing apredetermined amount in response to a physical factor such as anelectrical current or transfer of thermal energy or a mechanical input.

In another embodiment as shown in FIG. 16, which is a longitudinalcross-sectional view of the stent 1400 illustrated in FIG. 14 in abiodegraded condition, the occlusive element 1412 may biodegrade toproduce an enlarged channel 1414 within the occlusive element 1412through which vessel flow may travel. As the channel 1414 graduallywidens, the occlusion factor decreases proportionally. In an aspect, theocclusive element 1412 may be designed to biodegrade at a steady andpredetermined rate, resulting in a gradual increase in vessel flowvelocity according to a predetermined schedule. In another aspect, theocclusive element 1412 may be formed into an expandable structure suchas an iris-type structure, wherein the expandable structure is designedto slowly expand according to a predetermined schedule, resulting in thegradual increase of vessel flow through the stent 1400. The dissolutionand/or expansion of the occlusive element may occur spontaneously, or inresponse to exposure to a physical and/or chemical agent that triggersthe dissolution or expansion. In an aspect, the dissolution and/orexpansion of the occlusive element 1412 may occur in response toexposure to an injected medium introduced into the vessel 114 upstreamof the stent 1400.

In an aspect, the occlusive element 1412 may biodegrade over a period oftime sufficient to allow for the healing of the vascular tissues injuredby the clot 116. The rate at which the occlusive element 1412biodegrades to reestablish flow within the vessel 114 may be specifiedusing a variety of methods discussed in detail herein below.

In an aspect, the interior and exterior surfaces of the stent 1400 maybe coated up to the full extent of the stent 1400 with a variety ofcoating materials including, but not limited to, biodegradablematerials, resorbable materials, clot-dissolving materials, and anyother known coating material suitable for use in an implantable stentdesign. In one aspect, the stent 1400 may be partially or fully coatedto facilitate in the compression of a clot or other structure, resultingin the reestablishment of physiological vessel flow.

In another aspect, the occlusive element 1412 may incorporatebiodegradable and/or bioresorbable materials in a configuration designedto biodegrade at a predetermined rate. In an aspect, the occlusiveelement 1412 may be constructed partially of biodegradable and/orbioresorbable materials with additional non-biodegradable structuralelements such as cross members, a mesh, and/or a screen. In otheraspects, the occlusive element 1412 may be constructed entirely ofbiodegradable and/or bioresorbable materials. The dimensions and designof the occlusive element 1412 may be selected based on one or more of atleast several factors including, but not limited to the desireddissolution rate, the desired structural integrity of the stent 1400,the ease of deployment and collapse of the stent 1400 in use, and anyother relevant factor.

iii. Hybrid Devices

In other additional aspects, the vessel flow control device may includeany combination of any number of external flow control devices andimplantable flow control devices without limitation. For example, thevessel flow control device may include an external flow control devicesuch as an external clamp and an implantable flow control device such asa stent device. In another example, the vessel flow control device mayinclude a stent device as well as a balloon device in combination.

II. Methods of Using Vessel Flow Control Device

The vessel flow control device may be used to treat an afflicted regionof a patient using methods described herein below in various aspects. Inone aspect, a vessel flow control device is situated in a vessel of apatient upstream of the afflicted region and configured to an occlusionfactor of essentially 100%, resulting in the essentially completeobstruction of the vessel flow to the afflicted region. As the afflictedregion recovers, the occlusion factor of the vessel flow control devicemay be gradually decreased, resulting in a gradual increase in vesselflow and/or vessel pressure in the afflicted region. This gradualdecrease of the occlusion factor may be specified using any one of atleast several control methods. Non-limiting examples of suitable controlmethods include: autonomous device-based adjustments such as thedissolution of obstructive materials in the device as described hereinabove; manual adjustment by a medical practitioner; automated adjustmentof the vessel flow according to a predetermined schedule; and/orautomated adjustment of the vessel flow based on commands from afeedback control system.

a. Treatment Algorithm

A procedure for treating an afflicted region of a patient using a vesselflow control device is provided in one aspect. A flowchart 1000illustrating the steps of the procedure is provided in FIG. 9. In thisaspect, a delivery device with the attached vessel flow control devicemay be inserted into the vessel of the patient at step 1002. After thedelivery device has been inserted, the flow control device may besituated upstream of the afflicted region of the patient at step 1004.The flow control device may then be deployed to occlude the vessel andstop blood flow to the afflicted region. In this aspect, the flowcontrol device may be deployed to an occlusion factor of about 100% fora predetermined time at step 1006. Once the flow control device has beencompletely deployed, the occlusion factor of the flow control device maybe reduced by about 1% to restore some blood flow past the flow controldevice to the afflicted area at step 1008. The afflicted region may thenbe monitored for vascular leakage for a predetermined period, as shownin step 1010.

In this aspect, the occlusion factor and vascular leakage may beassessed and this information may be used to determine any adjustmentsto be made to the occlusion factor of the device to increase or decreasethe flow to the vessel. If the occlusion factor is determined to be notequal to 100% or 0% at step 1012 and if there is no vascular leakage atstep 1014, then the occlusion factor of the flow control device may bereduced by another 1% at step 1016 to increase the blood flow in thevessel. After the reduction in the occlusion factor, the afflictedregion may again be monitored for vascular leakage at step 1010.

If the occlusion factor is not equal to 100% or 0% at step 1012 and ifthere is vascular leakage indicated at step 1014, then the occlusionfactor of the flow control device may be increased by about 1% at step1018 to decrease the flow through the vessel in order to stabilize thepatient or treatment. Steps 1010, 1014, 1016 and 1018 are repeated untilthe occlusion factor reaches either 100% indicating irreparable vesseldamage or 0%, indicating reestablishment of physiological flow in thevessel.

In this aspect, after step 1010, if the occlusion factor reaches 100% atstep 1012, and the duration of treatment indicated at step 1020 isgreater than a treatment window representing a maximum treatment timewithin which a favorable response is expected, then a permanent flowblocking device may be installed and the delivery device may be removedat step 1022. If the occlusion factor reaches 100% at step 1012, and theduration is not greater than the treatment window at step 1020, then theafflicted region may be monitored for vascular leakage for apredetermined period of time at step 1010 to assess whether thecondition of the vessel is improved. If the occlusion factor reaches 0%at step 1012, then the vessel is indicated as healed, and the deliverydevice and the flow control device may be removed at step 1024.

c. Methods of Monitoring Blood Flow

In various aspects, the adjustments to the vessel flow rate during thetreatment of an afflicted region of a patient may be influenced bymeasurements obtained to monitor the blood flow within the afflictedregion. For example, measurements that detect vascular leakage withinthe afflicted region may indicate the need to decrease the vessel flowby increasing the occlusion factor of the device.

Blood flow in the vicinity of the vessel flow control device andvascular leakage may be monitored during treatment using any knownmethod. Non-limiting examples of suitable methods for monitoring bloodflow and vascular leakage include: angiogram, ultrasound, Dopplerultrasound, computed tomography (CT), magnetic resonance imaging (MRI),magnetic resonance angiography (MRA), heat transfer, patientneurological tests, and/or any other method of monitoring blood flowknown in the art. In an aspect, an angiogram may be used to monitorblood flow by injecting a contrast medium from a delivery device such asa catheter and measure the rate of movement of the contrast medium downthe vessel. Ultrasound may be used in an aspect to directly image bloodflow or may be used as an ultrasonic flow meter by measuring the transittime between pulses from ultrasound transducers in opposite direction.In another aspect, Doppler ultrasound may utilize the change in pitch ofreflected sound waves off of moving blood cells to measure blood flow.CT or computerized axial tomography (CAT) may be used with or without acontrast agent to measure blood flow by comparing sequential scans. Insome aspects, CT and/or CAT may be used with xenon or positron emissiontomography (PET) for enhanced imaging. In yet another aspect, MR may beused to track blood flow including, but not limited to, instant MRI,functional MRI, or MR angiography. The measurement of heat loss of adevice in the blood stream may measure the flow of blood past the devicein one aspect.

d. Control Methods

The occlusion factor of the vessel flow control device may be increasedor decreased to control flow in vessels using any of the methods andstructures described herein previously. Non-limiting examples of methodsof controlling blood flow and the occlusion factor of the device includeautonomous device-based adjustments, manual adjustments, programmableadjustments, and feedback control adjustments.

In an aspect, the vessel flow control device may incorporate featuresand materials that result in the gradual decrease in occlusion factordue to the intrinsic properties of the device 100. In an aspect, theflow control device 100 may be constructed of a material that may losepressure or biodegrade at a constant rate, including, but not limitedto, a biodegradable material, a porous material, urethane, or any othermaterial known in the art. In another aspect, the flow control device100 may be made of a material that may have an adjustable osmosis rate.In this aspect, various materials may be flushed over or inside the flowcontrol device 100 to change the deflation rate and alter the occlusionfactor. In an aspect, the pressure losses within the device may be usedto alter the occlusion factor of the device as described hereinpreviously.

In another aspect, the occlusion factor of the device may be manuallycontrolled. FIG. 17 is a schematic diagram illustrating the manualcontrol of the occlusion factor of the vessel flow device 100 by amedical practitioner 1704. After the vessel flow control device 100 issituated within a vessel 114 upstream of an afflicted region 112 of apatient 1702, a medical practitioner 1704 may manually adjust theocclusion factor of the device 100 using a manual adjustment apparatus1706 such as an adjustment syringe as illustrated in FIG. 17. Themedical practitioner 1704 may monitor the vessel flow in the afflictedregion 112 using one or more measurements 1708 described hereinpreviously, such as ultrasound or MRI imaging.

For example, the medical practitioner 1704 may manually decrease theocclusion factor of the device 110 after observing measurements 1708that indicate normal vessel flow in the afflicted area 112. This manualadjustment results in increased vessel flow through the afflicted region112. The medical practitioner 1704 may continue to monitor themeasurements 1708 and make additional manual adjustments to theocclusion factor of the device 100 using the manual adjustment apparatus1706 as needed.

In this aspect, manual adjustment methods may include, but are notlimited to, manipulating fine adjustment syringes and/or stop-cocks tocontrol the decrease or increase of the occlusion factor of the flowcontrol device 100. In another aspect, manual adjustment may use fixedrate/flow items to control the decrease or increase of the occlusionfactor of the flow control device. The blood flow may change in thisaspect by manually adjusting the constant leak rate of the flow controldevice, resulting in a constant increase or decrease in the occlusionfactor of the flow control device. In another aspect, the blood flow maybe controlled by the use of a manual flow, osmosis, or a leak ratedevice that may be attached to the flow control device to controlremoval of fluid from the flow control device to increase or decreasethe occlusion factor.

A programmable device may be used to control blood flow and the increaseor decrease of the occlusion factor of the flow control device inanother aspect. FIG. 18 is a schematic diagram illustrating a method ofcontrolling the occlusion factor of the vessel flow control device 100using a programmable device 1802 in an aspect. In this aspect, theprogrammable device 1802 may send a series of control signals to anautomated adjustment device 1804. In response to the series of controlsignals received from the programmable device 1802, the automatedadjustment device may implement the adjustment of the occlusion factorof the device 100. In another aspect, the series of control signalsgenerated by the programmable device 1802 may be specified, adjusted,and/or manually input into the programmable device 1802 by the medicalpractitioner 1402. For example, the medical practitioner 1402 may selecta more gradual rate of adjustment implemented by the programmable device1802.

The programmable device 1802 may include CPU, processors, and computerreadable media that execute stored commands and/or algorithms toimplement a series of adjustments to the occlusion factor of the vesselflow control device 100 according to a predetermined schedule. Theprogrammable device 1802 may use a predefined adjustment rate that mayfollow a pre-stored rate of blood flow or pressure increase or decrease.In an aspect, the programmable device 1802 may follow a programmable butdefined rate of change. A motorized syringe or other adjustment device1804 may be used to increase or decrease the occlusion factor at aconstant fixed rate in one aspect. An electronic syringe or adjustmentdevice 1804 in an aspect may allow multiple pre-stored changes to stopand start a constant or fixed rate flow control device 100 to increaseor decrease the occlusion factor.

In another embodiment, a feedback control system may be used to controlthe blood flow or pressure using feedback from measured signs andsymptoms from the patient. In an aspect, external patient metrics may beused to automatically change the rate of increase or decrease of theocclusion factor of the flow control device and change the correspondingblood flow/pressure. In another aspect, internal vascular patientmetrics and/or patient signs and symptoms may automatically change therate of increase or decrease of the occlusion factor of the flow controldevice and change the corresponding blood flow/pressure.

FIG. 19 is a schematic diagram illustrating the control of the occlusionfactor of the vessel flow control device 100 using a feedback controldevice 1902. The feedback control device 1902 may include CPU,processors, and computer readable media that execute stored commandsand/or algorithms to implement a series of adjustments to the occlusionfactor of the vessel flow control device 100 based on measuredquantities related to blood flow within the afflicted area 112 asdescribed herein above. For example, the feedback control device 1902may execute stored instructions to implement a control algorithm similarto the algorithm described herein above and illustrated in FIG. 9.

Referring back to FIG. 19, the measured quantities received by thefeedback control device 1902 may be obtained by external measurementdevices 1708 such as ultrasound and/or MRI imaging, and optionally bymeasurements obtained by internal instrumentation 1904 such as heatedflow rate sensors or piezoelectric pressure sensors as describedpreviously herein. The feedback control device 1902 processes themeasured quantities received from the external measurement devices 1708and/or internal instrumentation 1904, and transmits a control signal tothe adjustment device 1804, which implements the adjustment of theocclusion factor of the vessel flow control device 100. In anotheraspect, the medical practitioner 1704 may manually input, override,and/or modify the control commands transmitted by the feedback controldevice 1902.

a. Treatment of Ischemic Stroke

In an aspect, the method described herein above may be used to treat anischemic stroke in a mammalian patient. In this aspect, the vessel flowcontrol device may be situated within a brain circulatory vesselupstream of an ischemic region. The vessel flow control device maycompletely occlude the vessel flow while a clot situated downstream ofthe vessel flow control device is removed. In one aspect, the vesselflow control device may be a dual balloon device implanted such that theclot is situated between the distal balloon and the proximal balloon ofthe dual balloon device. The dual balloon device may further administerclot-dissolving compounds and/or other treatments to reduce or eliminatethe clot from the brain blood vessel. The method described herein abovemay then be used to gradually restore blood flow, while preventinghemorrhaging of the brain circulatory vessel during the recovery of thepatient.

b. Treatment of Tumors

In an aspect, the method described herein above may be used to enhancethe effects of chemotherapeutic compounds against tumor cells and/ortissues. In an aspect, the vessel flow control device may be situatedwithin a circulatory vessel responsible for supplying blood to the tumorcells and/or tissue. The vessel flow control device may be configured toreduce the blood flow to the tumor cells and/or tissue, resulting in theshrinkage of the tumor. Upon removal of the tumor, the vessel flowcontrol device may be configured to enhance the blood flow to thetissues surrounding the excised tumor, thereby enhancing the recovery ofthis surrounding tissue.

c. Treatment of Other Disorders

In an aspect, the method described herein above may be used to enhancethe treatment of other disorders including, but not limited to diabetes,aneurisms, stenosis dissolutions, arterial repairs, and any otherdisorder that may benefit from controlled vessel flow and/or drugrelease. In an aspect, the occlusion of vessel flow may be coupled withthe release of a therapeutic compound in order to lengthen the dwelltime of the compound in the vicinity of the target cells and/or tissues.In addition, the vessel flow may be increased after a predeterminedtreatment time to enhance the removal of the compound from the vessel ofthe patient.

The foregoing merely illustrates the principles of the invention.Various modifications and alterations to the described embodiments willbe apparent to those skilled in the art in view of the teachings herein.It will thus be appreciated that those skilled in the art will be ableto devise numerous systems, arrangements and methods which, although notexplicitly shown or described herein, embody the principles of theinvention and are thus within the spirit and scope of the presentinvention. From the above description and drawings, it will beunderstood by those of ordinary skill in the art that the particularembodiments shown and described are for purposes of illustrations onlyand are not intended to limit the scope of the present invention.References to details of particular embodiments are not intended tolimit the scope of the invention.

What is claimed is:
 1. A method for treating a patient having a vessel,the method comprising: receiving a delivery device in an internal volumeof a variable occlusion element, the internal volume enclosed by aninner member and opening to a proximal opening disposed at a proximalend of a balloon body and a distal opening disposed at a distal end ofthe balloon body, the delivery device positioning the variable occlusionelement in a lumen of the vessel; enlarging a toroidal volume as thevariable occlusion element inflates, the toroidal volume enclosed by anouter membrane of the balloon body, the outer membrane sealed to theinner member at the proximal end and the distal end; and shrinking thetoroidal volume as the variable occlusion element deflates, the toroidalvolume enlarging or shrinking as the variable occlusion element inflatesor deflates between a plurality of occlusion states, each of theplurality of occlusion states including an occlusion factorcorresponding to a percentage of a cross-sectional area of the lumen ofthe vessel occluded by the variable occlusion element.
 2. The method ofclaim 1, wherein the occlusion factor is controlled by a feedback. 3.The method of claim 2, wherein the feedback is at least one of apressure or a flow of the vessel.
 4. The method of claim 1, wherein, theouter membrane has a shape dictated by the occlusion factor.
 5. Themethod of claim 1, wherein the percentage ranges from 5 percent to 100percent.
 6. The method of claim 1, wherein the variable occlusionelement selectively transitions between the plurality of occlusionstates.
 7. The method of claim 1, wherein a subsequent occlusion stateof the plurality of occlusion states includes a lower occlusion factorthan a current occlusion state when a measurement of vascular leakageindicates no vascular leakage and the subsequent occlusion stateincludes a higher occlusion factor than the current occlusion state whenthe measurement of vascular leakage indicates vascular leakage.
 8. Themethod of claim 1, wherein a second balloon body is arrangedsequentially with the balloon body, the balloon body and the secondballoon body being hydraulically independent of each other.
 9. Themethod of claim 1, wherein the delivery device includes at least one ofa guide wire or a catheter.
 10. The method of claim 9, wherein thecatheter controls vessel flow through the variable occlusion elementwhen the occlusion factor is fully occluded.
 11. The method of claim 1,wherein the delivery device controls the toroidal volume by providingpneumatic pressure to inflate or deflate the variable occlusion element.12. The method of claim 1, wherein the balloon body is made of asemipermeable material, the semipermeable material permitting passivemovement of fluid through the variable occlusion element.
 13. The methodof claim 1, wherein the delivery device includes a conduit disposedrelative to the body, the conduit directing at least one substance intothe lumen of the vessel downstream of the variable occlusion element.14. A method of controlling a blood flow within a lumen of a vesselcomprising: positioning a variable occlusion element in the lumen by adelivery device; deploying the variable occlusion element to anocclusion factor of 100%; deflating the variable occlusion element bydecreasing the occlusion factor over a time period, the occlusion factorbeing controlled by a feedback.
 15. The method of claim 14, wherein thefeedback is a pressure and flow of the vessel.
 16. The method of claim14, wherein the feedback is based on a manual command.
 17. The method ofclaim 14, wherein the variable occlusion element is made of asemipermeable material configured to allow the passive movement of fluidinto or out of the at least one variable occlusion element.
 18. Themethod of claim 14, wherein the feedback is automatic.
 19. The method ofclaim 14, wherein the variable occlusion element includes one or moreballoons.
 20. The method of claim 14, wherein the variable occlusionelement selectively transitions between a plurality of occlusion states.